Association of GLP1 Analogues and SGLT2 Inhibitors With the Risk of Osteoarthritis in Type 2 Diabetic Patients

Osteoarthritis (OA) is a multifactorial joint disease related to multiple inflammatory pathways which are triggered by mechanical and cellular stress, leading to increased production of pro-inflammatory mediators, reactive oxygen species, advanced glycation end products (AGEs). These mediators promote the release of proteolytic enzymes, which degrade the cartilage matrix. A recent study emphasized on the relation between metabolic syndrome and OA, considering metabolic dysregulation as a major factor in OA progression.

GLP-1 receptor agonists lower blood sugar by boosting glucose-dependent insulin release, reducing glucagon secretion, and slowing stomach emptying. GLP-1RA is present in both healthy and osteoarthritic cartilage, indicating a direct effect on chondrocytes. so it can decrease the accumulation of AGEs, which is the main cause of OA. It also reduces appetite, leading to weight loss which decreases the mechanical stress on joints. GLP downregulates proinflammatory cytokines (IL-6, TNF-a). also inhibits NF-κB pathway. which has a role in promoting osteoclast formation, so GLP plays a protective role in OA.